Technologies capable of biological sensing can offer substantial advances in the medical diagnostics field by introducing the capacity to detect molecular targets in a label-free and rapid format. Current methods used for biological sensing utilize fluorescence, calorimetric, or surface plasmon resonant techniques as indicators of a successful molecular recognition event and are thus not amenable for use by non-technical operators.
While these methods are main-stream in their respective adoption for the molecular diagnostics arena, they are not without functional limitation. For fluorescence monitoring and Enzyme Linked Immunosorbent Assay [ELISA], superfluous tags must be conjugated to the desired target through the mechanism of additional labeled antibodies, thus adding necessary complexity and cost. Colorimetric assays require the generation of a color change, often mediated via an enzymatic mechanism, and are thus non-ideal for generating high density arrays.
Miller et al. in PCT Application WO 03/036225 A1, filed May 1, 2003, sets forth a device that enables the label-free detection of biomolecules. The Miller sensing system is functionally bipartite and is comprised of: 1) a receptor for at least one target, the receptor including a substrate and a transparent coating on the substrate having front and back surfaces; and 2) a light source positioned to direct at least a portion of the light from the light source toward the coating on the receptor; and a detector positioned to capture the light reflected from the front and back surfaces of the coating, where the detector identifies the presence of at least one target based on the change in the interference pattern of the captured light.
However, the Miller system does not lend itself to quantitative detection of biomolecules in high density receptor arrays. Therefore, the need remains for the label-free detection of biomolecules, wherein a resulting image allows for quantitative analysis.